首页 > 资讯 > FDA支持药品研发中采取灵活手段的理由

出自识林

2014-02-24 FDA Voice

大家都知道人各有异，同样每种疾病每种药品也是不同的。

所以我们对于《美国医学会杂志》（JAMA）公布的一项最新研究结果并不惊讶。这项研究显示，在2005年到2012年期间，在审批用于208种适应症的188种新治疗药品时，FDA使用一系列不同的临床试验证据。这一结果与我们近期的监管指令完全相符。我们相信用临床研究的不同方法支持药品批准是一个好消息而非坏消息。

用于支持这项药品批准研究的数据是基于每种适应症两项关键性临床试验的中位数。关键性试验提供FDA用于决定是否批准一个药品的最为重要的数据。

但是作者更仔细的观察发现，其中超过三分之一的药品是基于单个关键性临床试验获批，同时还涉及的临床试验仅有较小的受试组，用时也较短。在所研究的审批中，新药的试验用时仅为现有市售药品试验用时的约40%。

基于上述结果，作者得出结论认为， FDA达成批准的方法“在彻底性方面变化较大”。或者，用一位参与这项研究的作者的话讲：“FDA的批准并非生而平等”。尽管我并不认为这是作者的真实意图，但许多评论者却将此放大为批评。但是如果FDA使用一个严格的“一刀切”的方法，我将感到更为困惑。

患有严重的或危及生命的病症的患者，尤其是缺少好的可选疗法的患者，反复告诉我们他们希望做出一定权衡以得到治疗。

当然，“彻底性”一词，譬如一项临床试验是否足够大，在旁观者眼中，是仁者见仁，智者见智。没有理由期望不论任何疾病，都要求在数量相近的患者中开展试验。

临床研究手段的丰富显示FDA对药品研发与审批采取创新与灵活的手段。国会于1997年批准的《食品药品管理现代化法案》（FDAMA）以及最近于2012年批准的《食品药品管理安全与创新法案》（FDAISA），特别认可了这种手段。

现在FDA与新药申请人一起为每个药品设计研发与审评路径，以期最好地反映疾病特点以及有意接受治疗的患者需求。进入我们考量中的一些因素，包括该药品是否治疗了一种罕见或严重疾病或解决了任何未被满足的需求，以及之前我们可能对该药品有所了解。

因此，以FDA去年批准的Imbruvica （依鲁替尼）为例，这种套细胞淋巴瘤治疗用药的获批，是基于一项“开标、单臂临床试验”，这意味着所有参与临床试验的患者均使用这种药品，而且患者与研究者都知道他们使用了什么药品。该结果被用于与111名参与临床试验患者与之前针对疾病治疗的应答相比较。

而对于戈谢病的罕见病用药Elelyso（taliglucerase alfa），在2012年仅基于56名患者的两个试验获批。

相比之下，一些实验需要更大数量的患者，以证明药品的作用。此类情况常见于慢性病症如心血管疾病患者的研究，研究较大的样本量有助于捕捉到治疗效果。

无论选择了何种临床试验设计，对于所有寻求在美国上市的药品，FDA始终遵循相同的法定审批标准。

增加灵活性并不意味着放弃标准，当然也不意味着放弃科学性。恰恰相反，在寻找解决我们所面临挑战的创造性解决方案的过程中，我们需要应用先进的科学，提升效率、产出率和我们共同的能力。

最后要说的是，这就是明智规制—— 确保患者可以更快获得科学所能提供的最好疗法。

FDA局长 - Margaret A. Hamburg医学博士 - 2014-02-06
校译：识林-Kapok 2014-02-22

Why FDA Supports a Flexible Approach to Drug Development
Posted on February 6, 2014 by FDA Voice
By: Margaret A. Hamburg, M.D.

We all know that just as every person is different, so too is every disease and every drug.

Margaret Hamburg, M.D.And so we weren't surprised by the results of a new study published in the Journal of the American Medical Association. The study found that FDA used a range of clinical trial evidence when approving 188 novel therapeutic drugs for 208 indications (uses) between 2005 and 2012. These results are entirely consistent with our regulatory mandate. We believe varying approaches to clinical studies to support drug approval is good news, not bad.

Data to support the approvals studied were based on a median of two pivotal trials per indication. A pivotal trial presents the most important data used by FDA to decide whether to approve a drug.

But when the authors looked more closely, they found that more than a third of these drugs were approved on the basis of a single pivotal clinical trial, while still other trials involved only small groups of patients for shorter durations. Of the approvals studied, the new drug was compared with existing drugs on the market only about 40 percent of the time.

The authors concluded that, based on these results, the ways in which FDA arrived at those approvals “vary widely in their thoroughness.” Or, in the words of one study author, “Not all FDA approvals are created equally.” Although I don't think it was actually the author's intent, a number of commentators framed this as criticism. But I would be more troubled if FDA used a rigid, “one size fits all” approach.

People with serious or life-threatening illnesses, particularly those who lack good alternatives, have told us repeatedly that they are willing to make some trade-offs in order to gain access.

And, of course, “thoroughness,” such as whether a clinical trial is large enough, is in the eyes of the beholder. There is no reason to expect drugs to be tested on similar numbers of patients, regardless of the disease.

Variation in approach to clinical studies demonstrates FDA's innovative and flexible approach to drug development and approvals. Such an approach was specifically adopted by Congress in the Food and Drug Administration Modernization Act in 1997 and, most recently, in the Food and Drug Administration Safety and Innovation Act in 2012.

The FDA of today works with sponsors of new drugs to design a development and review pathway for each drug that best reflects the disease and patients it is intended to treat, the drug itself, and other treatment options. Some of the factors that enter into our calculus include whether the drug treats a rare or serious disease or addresses an unmet need and any previous knowledge we might have about the drug.

Thus, for example, FDA approved Imbruvica (ibrutinib), a treatment for mantle cell lymphoma, last year based on an “open-label, single-arm trial,” which means that every patient received the treatment and both patients and researchers knew they were receiving it. The results were compared to how well the 111 participating patients had responded to previous treatment for their disease.

And Elelyso (taliglucerase alfa) – for Gaucher disease – was an orphan drug approved in 2012 based on two trials with 56 patients.

In contrast, some trials require large numbers of patients to demonstrate a drug's effects. This is often the case in studies in patients with a chronic condition such as cardiovascular disease, where larger populations are studied to capture treatment effects.

No matter what clinical trial design is chosen, the Agency always applies the same statutory approval standards of safety and efficacy to all drugs seeking to be marketed in the United States.

Increased flexibility does not mean abandoning standards, and it certainly does not mean abandoning science. Just the opposite. We need to employ the best science in ways that will increase efficiency, productivity and our shared ability to find creative solutions to the challenges that confront us.

At the end of the day, that is just smart regulation – ensuring that patients can more rapidly have access to the best that science has to offer.